1. Field of the Invention
The field of this invention is methods and compositions that increases retrievable fluid and cellular material from a breast duct.
2. Description of the Background Art
For several decades significant members of the medical community dedicated to studying breast cancer have believed and shown that the cytological analysis of cells retrieved from nipple discharge from the breast milk ducts can provide valuable information leading to a identifying patients at risk for breast cancer. Indeed Papanicolaou himself contributed to the genesis of such a possibility of a “Pap” smear for breast cancer by analyzing the cells contained in nipple discharge. See Papanicolaou et al, “Exfoliative Cytology of the Human Mammary Gland and Its Value in the Diagnosis of Cancer and Other Diseases of the Breast” Cancer (1958) March/April 377-409. See also Petrakis, “Physiological, biochemical, and cytological aspects of nipple aspirate fluid”, Breast Cancer Research and Treatment 1986; 8:7-19; Petrakis, “Studies on the epidemiology and natural history of benign breast disease and breast cancer using nipple aspirate fluid” Cancer Epidemiology, Biomarkers and Prevention (January/February 1993) 2:3-10; Petrakis, “Nipple Aspirate Fluid in epidemiological studies of breast disease”, Epidemiologic Reviews (1993) 15:188-195. More recently, markers have also been detected in nipple fluid. See Sauter et al, “Nipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer risk”, British Journal of Cancer 76(4):494-501 (1997). The detection of CEA in fluids obtained by a nipple blot is described in Imayama et al. (1996) Cancer 78: 1229-1234.
Cytological and other analysis of breast ductal fluid that has been made for decades uses nipple aspirate fluid (NAF) collected from the nipple surface upon aspiration of the nipple. Nipple aspiration of the breast yields fluid in the female population in about half the women tested. The fluid retrieved from nipple aspiration has usually several ductal epithelial cells and sometimes as many as 15 or 20 ductal epithelial cells for analysis. Rarely are clumps (groups of about 6 to 10 or more cells) of ductal epithelial cells retrieved by NAF. It is generally believed that NAF pulls fluid from the upper reaches of the ductal network, and usually not more than a cc or so of this fluid is collected at a time. NAF is collected from the nipple surface and cannot consistently be tied to the particular duct from which the aliquot was secreted due to the fact that several ducts can yield fluid and are thus pooled in any given nipple aspiration. Because so few cells are retrieved in NAF, often the fluid, material and/or cell numbers retrieved are insufficient for analysis.
Ductal fluid has been retrieved during galactography, a procedure that is performed upon a condition of spontaneous nipple discharge. Galactography is performed in order to identify the cause of the discharge. In a galactography procedure, a small amount of ductal fluid is collected in an open lumen needle or cannula by syringe-controlled aspiration. This fluid and cell amount is generally about equivalent to NAF yields. Syringe-controlled aspiration with a cannula or lumen in a non-spontaneously discharging duct can result in a collapsed duct that results in no or very little fluid or cell yield. It is presumed that the small amount of fluid retrieved before or after a galactography procedure is retrievable because the duct is full of fluid (and therefore spontaneously discharging). Occult conditions not manifesting spontaneous discharge from the duct do not generally provide an opportunity for intraductal fluid withdrawal.
A non-spontaneously yielding duct can be identified as a high-risk by preliminary nipple aspiration because high-risk ducts tend to yield fluid upon NAF, and these ducts can be accessed with a ductal access tool. The accessed duct can be infused with a biocompatible fluid that mixes with the ductal fluid and cells and other markers. The filled duct can then support aspiration, withdrawal, or otherwise collection of some of this fluid that comprises ductal fluid, ductal epithelial cells, and/or other markers of the breast duct condition.
It would be advantageous to an analysis of breast conditions, particularly assymptomatic occult breast conditions to increase the retrievable fluid and/or cells in one or more ducts in a breast in preparation for a subsequent intraductal access of one or more of these ducts. In addition, increased fluid in the duct provides the opportunity to capture and generate sloughing cells and other markers within the duct.